PXD043496

PXD043496 is an original dataset announced via ProteomeXchange.

Title	G-CSF reshapes the cytosolic PCNA scaffold and modulates glycolysis in neutrophils
Description	The balance between neutrophil survival and apoptosis must be tightly regulated to avoid exaggerated inflammatory responses. Cytosolic proliferating cell nuclear antigen (PCNA) is involved in neutrophil survival and function, where it acts as a scaffold and associates with proteins involved in NADPH oxidase activation, cytoskeletal dynamics and metabolism. While the PCNA interactome has been characterized in neutrophils under homeostatic conditions, less is known about neutrophil PCNA in pathophysiological contexts. G-CSF is a cytokine produced in response to inflammatory stimuli, that regulates many aspects of neutrophil biology. Here we used neutrophils from G-CSF-treated haemopoietic stem cell donors (GD) as a model to understand the role of PCNA during inflammation. Proteomic analysis of the neutrophil cytosol revealed significant differences between GD and healthy donors (HD). PCNA was one of the most upregulated proteins in GD and the PCNA interactome was significantly different in GD compared to HD. Importantly, while PCNA associated with almost all enzymes involved in glycolysis in HD, these associations were decreased in GD. Functionally, neutrophils from GD had a significant increase in glycolysis compared to HD. Using p21 competitor peptides, we showed that PCNA negatively regulates neutrophil glycolysis in HD, but had no effect on GD neutrophils. These data demonstrate that G-CSF alters the PCNA scaffold, affecting interactions with key glycolytic enzymes and thus regulates glycolysis, the main energy pathway utilized by neutrophils. Taken together, we show PCNA is a key protein involved in neutrophil survival and glycolysis and may be instrumental in the reprogramming that neutrophils undergo in inflammatory or tumoral settings.
HostingRepository	PRIDE
AnnounceDate	2024-02-15
AnnouncementXML	Submission_2024-02-15_03:14:51.071.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Virginie Salnot
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-03 07:38:39	ID requested
⏵ 1	2024-02-15 03:14:52	announced

10.1093/jleuko/qiad122;

Aymonnier K, Bosetta E, Leborgne NGF, Ullmer A, Le Gall M, De Chiara A, Salnot V, Many S, Scapini P, Wicks I, Chatfield S, Martin KR, Witko-Sarsat V, G-CSF reshapes the cytosolic PCNA scaffold and modulates glycolysis in neutrophils. J Leukoc Biol, 115(2):205-221(2024) [pubmed]

submitter keyword: PCNA, neutrophil, survival, G-CSF, glycolysis

Véronique Witko-Sarsat
contact affiliation	INSERM U1016, CNRS UMR 8104, Université Paris Cité, Cochin Institute, Paris, France
contact email	veronique.witko@inserm.fr
lab head
Virginie Salnot
contact affiliation	3p5-proteom'ic plateform
contact email	virginie.salnot@parisdescartes.fr
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2024/02/PXD043496

PRIDE project URI

• PRIDE
  1. PXD043496
     1. Label: PRIDE project
     2. Name: G-CSF reshapes the cytosolic PCNA scaffold and modulates glycolysis in neutrophils